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Article Dans Une Revue OncoImmunology Année : 2021

Phased differentiation of γδ T and T CD8 tumorinfiltrating lymphocytes revealed by single-cell transcriptomics of human cancers

Résumé

γδ T lymphocytes diverge from conventional T CD8 lymphocytes for ontogeny, homing, and antigen specificity, but whether their differentiation in tumors also deviates was unknown. Using innovative analyses of our original and ~150 published single-cell RNA sequencing datasets validated by phenotyping of human tumors and murine models, here we present the first high-resolution view of human γδ T cell differentiation in cancer. While γδ T lymphocytes prominently encompass TCRVγ9 cells more differentiated than T CD8 in healthy donor's blood, a different scenario is unveiled in tumors. Solid tumors and lymphomas are infiltrated by a majority of TCRVγnon9 γδ T cells which are quantitatively correlated and remarkably aligned with T CD8 for differentiation, exhaustion, gene expression profile, and response to immune checkpoint therapy. This cancer-wide association is critical for developing cancer immunotherapies.
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Dates et versions

hal-03365502 , version 1 (05-10-2021)

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Juan-Pablo Cerapio, Marion Perrier, Camille-Charlotte Balança, Pauline Gravelle, Fréderic Pont, et al.. Phased differentiation of γδ T and T CD8 tumorinfiltrating lymphocytes revealed by single-cell transcriptomics of human cancers. OncoImmunology, In press, ⟨10.1080/2162402X.2021.1939518⟩. ⟨hal-03365502⟩
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